The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment.

Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modified PIEZO1-/- OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.

Overview on recent advances of magnetic metal-organic framework (MMOF) composites in removal of heavy metals from aqueous system.

Developing a novel, simple, and cost-effective analytical technique with high enrichment capacity and selectivity is crucial for environmental monitoring and remediation. Metal-organic frameworks (MOFs) are porous coordination polymers that are self-assembly synthesized from organic linkers and inorganic metal ions/metal clusters. Magnetic metal-organic framework (MMOF) composites are promising candidate among the new-generation sorbent materials available for magnetic solid-phase extraction (MSPE) of environmental contaminants due to their superparamagnetism properties, high crystallinity, permanent porosity, ultrahigh specific surface area, adaptable pore shape/sizes, tunable functionality, designable framework topology, rapid and ultrahigh adsorption capacity, and reusability. In this review, we focus on recent scientific progress in the removal of heavy metal ions present in contaminated aquatic system by using MMOF composites. Different types of MMOFs, their synthetic approaches, and various properties that are harnessed for removal of heavy metal ions from contaminated water are discussed briefly. Adsorption mechanisms involved, adsorption capacity, and regeneration of the MMOF sorbents as well as recovery of heavy metal ions adsorbed that are reported in the last ten years have been discussed in this review. Moreover, particular prospects, challenges, and opportunities in future development of MMOFs towards their greener synthetic approaches for their practical industrial applications have critically been considered in this review.

Self-assembly of multiscale anisotropic hydrogels through interfacial polyionic complexation.

Polysaccharides are explored for various tissue engineering applications due to their inherent cytocompatibility and ability to form bulk hydrogels. However, bulk hydrogels offer poor control over their microarchitecture and multiscale hierarchy, parameters important to recreate extracellular matrix-mimetic microenvironment. Here, we developed a versatile platform technology to self-assemble oppositely charged polysaccharides into multiscale fibrous hydrogels with controlled anisotropic microarchitecture. We employed polyionic complexation through microfluidic flow of positively charged polysaccharide, chitosan, along with one of the three negatively charged polysaccharides: alginate, gellan gum, and kappa carrageenan. These hydrogels were composed of microscale fibers, which in turn were made of submicron fibrils confirming multiscale hierarchy. Fibrous hydrogels showed strong tensile mechanical properties, which were further modulated by encapsulation of shape-specific antioxidant cerium oxide nanoparticles (CNPs). Specifically, hydrogels with chitosan and gellan gum showed more than eight times higher tensile strength compared to the other two pairs. Incorporation of sphere-shaped cerium oxide nanoparticles in chitosan and gellan gum further reinforced fibrous hydrogels and increased their tensile strength by 40%. Altogether, our automated hydrogel fabrication platform allows fabrication of bioinspired biomaterials with scope for one-step encapsulation of small molecules and nanoparticles without chemical modification or use of chemical crosslinkers.